THE THREE-DIMENSIONAL STRUCTURE OF HUMAN INTERLEUKIN-5Interleukin 5 (IL-5) is a specific cytokine involved in the development and differentiation of eosinophils. It plays an important role in diseases associated with increased levels of eosinophils, such as asthma and atopic dermatitis.',? W: have solved the three-dimensional structure of human 1L-5 to a resolution of 2.4 A using X-ray crystallographic techniques. The molecule is a dimer of identical subunits that are joined together by disulphide bridges. The crystal structure reveals a novel two-domain structure where each domain of the protein is a 4-helical bundle containing two short stretches of beta sheet. These domain structures show a high degree of similarity to the cytokine fold, which has already been described in Interleukin-2 and -4, granulocyte, and granulocyte-macrophage colony stimulating factors, and porcine and human growth hormones. This high degree of similarity within known cytokine structures has led us to make predictions of the structures of cytokines for which no three-dimensional information is available. Furthermore, it provides the molecular basis for the design of agonists and antagonists of IL-5, which will be important in the therapy of eosinophil mediated diseases.1L-5 is a T-cell-derived cytokine that causes eosinophilpoesis and activation of eosinophils. In order to investigate its biology and its role in models of asthmatic inflammation, we have produced the protein in large quantities. A synthetic gene for human IL-5 was overexpressed in E. coli, where the protein forms inclusion bodies. This protein can then be subsequently renatured under carefully controlled conditions of protein concentration and buffer redox potential to give large quantities of active p r~t e i n .~ Unlike the natural human IL-5, the E. coli derived material is not glycosylated. It is of equal potency, however, showing that glycosylation is not required for biological activity. We mapped the positions of the disulphide 118
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.